Final Flashcards

1
Q

How does a transporter reduce the activation energy in simple diffusion?

A

by forming non-covalent interactions with the dehydrated solute to replace the hydrogen bonding with water and by providing a hydrophilic transmembrane pathway.

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2
Q

What is the differences between channels and Active transporters?

A

Channels rate of flux is very fast and you cant saturate them. Once they open, anything can flow in/out. They are closed either by having a ligand bind or make it voltage-gated.
Transporters respond to the solutes they’re transporting by changing shape, whereas channels do not.

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3
Q

What are the conformations of the GLUT transporter?

A

T1, with the glucose-binding site exposed on the outer surface of the plasma membrane, and T2, with the binding site exposed on the inner surface.

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4
Q

What is the mechanism of glucose transport?

A
  1. Glucose in blood plasma binds to a stereospecific site on T1; this lowers the activation energy for
  2. a conformational change from glucoseout • T1 to glucosein • T2, affecting the transmembrane passage of the glucose.
  3. Glucose is released from T2 into the cytoplasm, and
  4. the transporter returns to the T1 conformation, ready to transport another glucose molecule.
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5
Q

Why do we not want glucose transport to max out in the liver?

A

We don’t want the glucose transporter to be maxed out in the liver b/c you want to be able to transport a large sum of glucose out of the cell into the muscles that need it

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6
Q

How is CO2 transported in Erythrocytes and lungs?

A

CO2 diffuses in and is converted to bicarbonate by carbonic anhydrase. We transport bicarb out and chloride in.
In the lungs, this process is reversed. The bicarb comes in from blood plasma and chloride is taken out.

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7
Q

What is the goal of the bicarb antiporter?

A

This cotransport system allows the entry and exit of HCO3- without changing the membrane potential. Its role is to increase the CO2-carrying capacity of the blood.

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8
Q

Why is energy needed in active transport?

A

Accumulation of solutes above an equilibrium point.

Endergonic deltaG is positive, thus it Requires energy to move solutes up a concentration gradient

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9
Q

what is the problem with vanadate?

A

Vanadate can bind, and block the P-Type ATPase, thus there will be no phosphorylation b/c the enzyme can only cleave a phosphate bond

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10
Q

What is the SERCA Pump?

A

an integral membrane protein that moves Ca2+ out of the cell membrane and into the ER lumen

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11
Q

What is the mechechanisum of the SERCA Pump?

A

Primary active transporter: ATP binds to its nucleotide domain, and then calcium comes in, but it gets stuck in the middle of the protein because it’s too big.
We hydrolyze ATP to ADP and phosphorylate the transporter and this changes its conformation, and the calcium is released into the lumen.
ADP falls off and becomes de-phosphorylated, and we change back into the original confirmation and do it the process again

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12
Q

What is the purpose of the Na/K+ ATPase?

A

Primary active antiporter that Maintains ECG in all our neurons by Pumping K against its concentration from inside the cell to out of the cell and sodium comes in.

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13
Q

What is the mechanism of Na/K+ ATPase?

A

In the absence of ATP, protein is facing inside the cell, and it likes sodium and it will pick up any sodium.
We phosphorylates and ATP binds and we change our confirmation and face outside, and now the protein hates sodium and it releases sodium.
so potassium will bind and then we will de-phosphorylate and change our confirmation, and we will do this back and forth creating an ECG

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14
Q

What is the role of ouabain?

A

With 2 sodium bound on the extracellular side, there is no way K+ can come in, de-establishing the electrical potential

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15
Q

What is the role of Palytoxin?

A

Locks protein so that ion-binding sites open on both sides, and K+ can exit, thus, it deflates the ion gradient

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16
Q

How does Digitalis work?

A

Digitalis is used to treat congestive heart failure (their heart isn’t pumping well enough so blood doesn’t flow well) by inhibiting sodium influx and raising sodium intracellular enough that the sodium-calcium pump when it transports it creates a much harder contraction

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17
Q

What are the parts of the F-type ATPase?

A
Fo = integral membrane protein complex
F1 = peripheral protein that uses the energy of ATP to drive protons uphill.
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18
Q

How is ATP generated generally in transport?

A

If you pumped proton to the mitochondrial matrix your hydrolyzing ATP and If you are pumping it out of the mitochondria, you are making ATP

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19
Q

What are ABC Transporters?

A

ATP-dependent transporters - Pump amino acids, peptides, proteins, metal ions, some lipids, bile salts out of cell against a concentration gradient.
2 nucleotide binding domains (NBD) and transmembrane
Most act as pumps, some act as ion channels that open and close with ATP hydrolysis.

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20
Q

What is the mechanism of ABC Transporter?

A

Substrate binds to the transporter on the cytoplasmic side, with ATP bound to the NBD sites.
On substrate binding and ATP hydrolysis to ADP, a conformational change exposes the substrate to the outside surface and lowers the affinity of the transporter for its substrate diffuses away from the transporter and into the extracellular space.

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21
Q

What is lactose permease?

A

a monomer secondary active transporter. Lactose permease is the transporter for lactose and is a transmembrane protein.
It transports one proton and one lactose into the cell. It is a symporter. The protons were established through the oxidative phosphorylation pathway

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22
Q

How does CN inhibit lactose permease?

A

CN binds to the last transporter of the ETC and inhibits the lactose permease
Lactose can still be transporter on the permease but it is a facilitated diffusion, and it will saturate easily b/c you cant get it across the membrane with CN inhibiting the establishment of the proton gradient

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23
Q

How else can lactose permease be inhibited?

A

We can also inhibit it by Arg and Glu which has a carboxylic acid and amino groups that can be protonated. Protons are transported by hoping across membrane by interacting with a proton. As the proton is coming through, it is binding to glut and arg changing the conformation, so lactose can come in really easily

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24
Q

Describe Glucose transporter in the intestinal cells?

A

Glucose is cotransported with Na+ across the apical plasma membrane into the epithelial cell. It moves through the cell to the basal surface, where it passes into the blood via GLUT2, a passive glucose uniporter. The Na+K+ ATPase continues to pump Na+ outward to maintain the Na+ gradient that drives glucose uptake.
sodium doesn’t affect the transporter b/c it’s not secondary active

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25
Q

How is water transported?

A

through Aquaporins; an Integral membrane protein with 4 monomers associated in a tetramer to form a pore

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26
Q

What is the purpose of NPA in the aquaporin ?

A

NPA = asparagine, proline, and alanine. Hydroxonium ion wouldn’t get close to this sequence. It helps the structure to filter out, so that only water come in and not any hydronium ions

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27
Q

What are the types of ion-selective channels?

A

Ligand-gated and Voltage-gated channels

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28
Q

How is K+ channel selective for only potassium?

A

Carbonyl groups line the walls of the pore of the selectivity filter to balance out the charge. 4 rigid protein groups form a selectivity filter, which makes the filtered highly selective for potassium over sodium ions

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29
Q

How does voltage-gated channel filter solutes?

A

When positively charged, the gate is open and sodium can come through. The channel will depolarize and the gates will close, and sodium cant go out

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30
Q

Why do we need ammonia channels?

A

We need ammonium channels b/c ammonia in water is usually charged and its NH4

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31
Q

How do toxins work?

A

they bind to voltage-gated sodium-potassium channels, disrupting the gradient

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32
Q

How does cystic fibrosis occur?

A

70% of patients have a deletion of a phenylamine (just 1) causing the protein to misfolded so it can’t insert into the membrane. The outer membrane becomes sticky because you don’t have water

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33
Q

What is oxidative phosphorylation?

A

Reduction of O2 to H2O in the mitochondria from Electrons donated by NADH or FADH2

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34
Q

What are the 3 stages of cellular respiration?

A

Stage 1: oxidation of fatty acids, glucose, and some amino acids yields acetyl-CoA.
Stage 2: oxidation of acetyl groups in the citric acid cycle includes four steps in which electrons are abstracted.
Stage 3: electrons carried by NADH and FADH2 are funneled into a chain of mitochondrial (or, in bacteria, plasma membrane-bound) electron carriers—the respiratory chain—ultimately reducing O2 to H2O. This electron flow drives the production of ATP.

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35
Q

How is ADP converted to ATP?

A

Electrons flow through a chain of membrane bound carriers
Free energy from the electron flow is coupled to the transport of protons across membrane.
Transmembrane flow of protons down their concentration gradient leads to synthesis of ATP.

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36
Q

What is needed of the membrane for ATP synthesis?

A

The membrane must contain proteins that couple the “downhill” flow of electrons in the electron-transfer chain with the “uphill” flow of protons across the membrane.
The membrane must contain a protein that couples the “downhill” flow of protons to the phosphorylation of ADP.

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37
Q

What is Ubiquinone?

A

Ubiquinone is a lipid-soluble conjugated dicarbonyl compound that readily accepts electrons
Upon accepting two electrons, it picks up two protons to give an alcohol –> ubiquinol

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38
Q

What is the sequence of electron carriers?

A

NADH/C1 to Q, Q to C3, C3 to Ctyo C, Cyto C to C4, C4 to O2

FADH2/C2 to Q, Q to C3, C3 to Cyto C, Cyto C to C4, C4 to O2

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39
Q

What happens in NADH/ubiquinone oxidoreductase/Complex I?

A

NADH becomes oxidized to NAD and its 2e’ gets transferred to Q and Q becomes QH2. complex 1 pumps 4 protons for every NADH that is oxidized

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40
Q

What is the difference between FADH2 and NADH

A

WHEN FADH2 GETS OXIDIED, YOU DON’T GET ANY PROTONS PUMPED CROSS, AND THUS IT DOESN’T allow you to make more ATP which is why NADH is a better
Ubiquinone is the branch point . If you start with FADH2 you don’t use complex 1, but if you’re using NADH you start at complex 1 and you will transfer the electrons to Q which becomes QH2 (ubiquinol)

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41
Q

What is Succinate Dehydrogenase/Complex II?

A

Q GOES TO QH2 TO REGENERATE FUMARATE BACK TO SUCCINATE TO CONTINUE THE CIRTIC ACID CYCLE
SUCCINATE DOES NOT PUMP PROTONS, ITS JUST TRYING TO regenerate FAD TO FADH2.

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42
Q

What is the role of heme in complex II?

A

The hemebis not on the main path of electron transfer but protects against the formation of reactive oxygen species (ROS) by electrons that go astray.

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43
Q

What is the role of Complex III/Ubiquinone: Cytochrome c Oxidoreductase?

A

Catalyzes the transfer of electrons from QH2 to oxidized cyt c.
Pump protons out of the mitochondrial matrix.

44
Q

What is the Q cycle?

A

Complex 3 gets QH2, and we drop one electron off to Cyto C and send the other down to Q which becomes a semiquinone and it gets stuck in the enzyme b/c we never release free radicals into the membrane. We have that C go away, and we have another QH2 that brings in another electron and reduce/send it to semiquinone sitting in the locked protein and now the semiquinone is allowed to be released. We used 1 QH2 to have 2 Cyot C reduced.

45
Q

What is the composition of complex IV?

A

Contains copper ions
CuA: two ions that accept electrons from cyt c
CuB: bonded to heme a3, forming a binuclear center that transfers four electrons to oxygen

46
Q

What is the mechanism of cytochrome oxidase?

A

We take 4 electrons to take one oxygen and make 2 waters. Step 1 cytochrome C binds to complex 4 and it drops off electrons and becomes oxidized.
That e comes to cytochrome B and we reduce the copper. The second electron comes sand we bind another cytochrome C, and re-reducing the iron cus its what binds oxygen (since we already have copper reduced).
Because we have copper close by, we can make a peroxide bridge, and we bind oxygen to the iron. We bring another electron and break the bond and we bring in a proton so it becomes a carboxyl.
Then we bring another electron to reduce the second oxygen, and 2 more protons will come in to release the water, thus we need all 4 electrons.
2 to get to the right reduction state and make the peroxide bridge, and 2 to break the peroxide bridge and make water. In this process, we have pumped 4 protons

47
Q

How is the proton-motive force generated?

A

actively transporting protons across the membrane - Complex I and Complex IV
chemically removing protons from the matrix - reduction of CoQ and reduction of oxygen
releasing protons into the inter membrane space - oxidation of QH2

48
Q

What is the proton motive force?

A

The inner mitochondrial membrane is impermeable to protons; protons can reenter the matrix only through proton-specific channels (Fo). The proton motive force that drives protons back into the matrix provides the energy for ATP synthesis, catalyzed by the F1 complex associated with Fo.

49
Q

What are the effect of oligomyocin in ATP synthesis?

A

If you inhibit ATP synthase with oligomyocin you stop ATP synthesis and oxidation

50
Q

What does DNP illustrate?

A

DNP is the uncoupling of oligomycin – it proves that we need protons on the other side of the membrane to keep oxidation going on without ATP

51
Q

What is the binding-change model ATP Synthase?

A

ATP cannot be released from one site unless and until ADP and Pi are bound at the other. Release ATP at O, and binds ATP at T state

52
Q

What occurs at subunit C and A in ATP Synthase?

A

There is an aspartate at the C subunit that will accept a proton. The minus it the aspartate when the C subunit hits the A subunit. The protonated aspartate causes the engine to move, and when it moves, one of the aspartate from the other C subunit comes into play

53
Q

What is the Stoichiometry between O2 consumption and ATP generation?

A

10 protons pumped outwards from NADH, and 3 flow inward to make 1 ATP, and 1 to get the ATP across the cytoplasm

54
Q

What is the malate-aspartate shuttle?

A

This shuttle for transporting reducing equivalents from cytosolic NADH into the mitochondrial matrix is used in liver, kidney, and heart.

  1. NADH in the cytosol enters the intermembrane space through openings in the outer membrane (porins), then passes two reducing equivalents to oxaloacetate, producing malate.
  2. Malate crosses the inner membrane via the malate–α-ketoglutarate transporter.
  3. In the matrix, malate passes two reducing equivalents to NAD+, and the resulting NADH is oxidized by the respiratory chain; the oxaloacetate formed from malate cannot pass directly into the cytosol.
  4. Oxaloacetate is first transaminated to aspartate, and
  5. aspartate can leave via the glutamate-aspartate transporter.
  6. Oxaloacetate is regenerated in the cytosol, completing the cycle.
55
Q

How is ADP transported into the matrix?

A

The adenine nucleotide translocase is an antiporter; the same protein moves ADP into the matrix and ATP out.
We also need to transport in phosphate via translocase (symporter) which is an active secondary transporter and the ATP antiporter is facilitated diffusion

56
Q

What ways is oxidative phosphorylation regulated?

A

Primarily regulated by substrate availability: NADH and ADP/Pi; Due to coupling both substrates required for electron transport and ATP synthesis
Inhibitor of F1 (IF1): Prevents hydrolysis of ATP during low oxygen; Only active at lower pH, encountered when electron transport it stalled (i.e., low oxygen)
Inhibition of OxPhos leads to accumulation of NADH - Causes feedback inhibition cascade up to PFK-1 in glycolysis

57
Q

What is the difference between an integral membrane protein and a hormone?

A

Receptor is an integral membrane protein except of hormone receptors. Hormones are steroids, steroids are lipids and they can come across the membrane because their receptors are already in the cell

58
Q

Examples of receptors

A

G protein−coupled receptors: epinephrine receptor
Enzyme-linked receptors: insulin receptor
Ligand-gated ion channels: nicotinic acetylcholine receptor
Nuclear receptors: steroid receptors

59
Q

What is specificity?

A

specific signal molecule fits binding site on its complementary receptor, and others don’t.

60
Q

What is amplification?

A

when enzymes activate enzymes, the number of affected molecules increases geometrically in an enzyme cascade.

61
Q

What is modularity?

A

proteins with multivalent affinities form diverse signaling complexed from interchangeable parts. phosphorylation provides reversible points of interaction.

62
Q

What is an adaptation?

A

receptor activation triggers a feedback circuit that shuts off the receptor or removes it from the cell surface

63
Q

What is integration?

A

when 2 signals have opposite effects on a metabolic characteristic such as the concentration of a second messenger, or the membrane potential Vm, the regulatory outcome results from the integrated input from both receptors

64
Q

How are membranes polarized?

A

The inside of the cell is typically negatively charged compared with the outside: Vm –50 to –70 mV.
The membrane potential is largely due to asymmetric transport of cations by Na+K+ ATPase: 3 Na+ out and 2 K+ in

65
Q

What is the mechanism of the Nicotin acetylcholine receptor?

A

When you bind acetylcholine, you open the channel and can bring in sodium and calcium flow in with their concentration gradient.
When its not bound, we have hydrophobic amino acids sitting around, and when acetylcholine bound, we have a conformation change and flip the charge of the amino acids and we have hydrophilic amino acids so sodium can come through.
Ligand is acetylcholine and the receptor is acetylcholine receptor

66
Q

How does the voltage and ligand-gated ion channels affect nerve signaling?

A

Nerve signals within nerves propagate as electrical impulses.
Propagation of the impulse involves opening of voltage-gated Na+ channels.
Opening of voltage-gated Ca++ channels at the end of the axon triggers the release of neurotransmitter acetylcholine.
Acetylcholine opens the ligand-gated ion channel on the receiving cell.

67
Q

How does the voltage-gated sodium channel work?

A

The four domains are wrapped about a central transmembrane channel lined with polar amino acid residues. The four pore regions come together near the extracellular surface to form the selectivity filter, which is conserved in all Na+ channels.
The filter gives the channel its ability to discriminate between Na+ and other ions of similar size. The inactivation gate closes soon after the activation gate opens

68
Q

What is the purpose of the tether ball?

A

How long the ball stays open depends on the length of the tether. Even though the channel is still open, the tether is plugged the whole so you cant get any sodium in, and that gives the sodium ATPase enough time to reestablish the CG

69
Q

Ion channels and nerve signaling

A

Initially, the plasma membrane of the presynaptic neuron is polarized (inside negative) through the action of the electrogenic Na+K+ ATPase, which pumps out 3 Na+ for every 2 K+ pumped in.

  1. A stimulus to this neuron causes an action potential to move along the axon, away from the cell body. The opening of a voltage-gated Na+ channel allows Na+ entry, and the resulting local depolarization causes the adjacent Na+ channel to open, and so on. The directionality of movement of the action potential is ensured by the brief refractory period that follows the opening of each voltage-gated Na+ channel.
  2. A split second after the action potential passes a point in the axon, voltage-operated K+ channels open, allowing K+ exit that brings about repolarization of the membrane (red arrow), to make it ready for the next action potential.
  3. When the wave of depolarization reaches the axon tip, voltage-gated Ca2+ channels open, allowing Ca2+ entry.
  4. The resulting increase in internal [Ca2+] triggers exocytic release of the neurotransmitter acetylcholine into the synaptic cleft.
  5. Acetylcholine binds to a receptor on the postsynaptic neuron (or myocyte), causing its ligand-gated ion channel to open.
  6. Extracellular Na+ and Ca2+ enter through this channel, depolarizing the postsynaptic cell.
70
Q

What is myathenia?

A

neuromuscular autoimmune disease. Treatment is injecting an esterase inhibitor because the acetylcholine receptor is covered by the antibody. If we inhibit the esterase, then the acetylcholine will stay around long enough to get a neurological response, so when the antibody falls off, the acetylcholine binds. We don’t know how to get rid of antibodies yet.
Insecticides disrupt the neurological charge Acetylcholine esterase degrades acetylcholine, and when broken down you have to re-synthesize it.

71
Q

insulin receptor

A

The insulin receptor (INSR) consists of two α subunits on the outer face of the plasma membrane and two β subunits that traverse the membrane and protrude from the cytosolic face.
Binding of insulin to the subunits triggers a conformational change that allows the autophosphorylation of Tyr residues in the carboxyl-terminal domain of the β subunits. Autophosphorylation further activates the Tyr kinase domain, which then catalyzes phosphorylation of other target proteins.

72
Q

What is insulin?

A

Insulin is a peptide hormone that is produced by the B-cells of islets of Langerhans in the pancreas.
Binding of insulin to the insulin receptor initiates a cascade of events that leads to increased glucose uptake and metabolism.
Inability to make or sense insulin -> diabetes

73
Q

How do we get GLUT4 into the membrane?

A

the phosphorylation/activating of PIP3 which binds to PKB which then is able to active another molecule to bind to RAF4 AND TAKE THAT OFF THE MOTOR WHICH WILL MOVE THE VESCILE INTO THE MEMBRANE

74
Q

glycogen synthase

A

Glycogen synthase phosphorylated = inactive, and active when de-phosphorylated. To keep GS from becoming inactive you have to inactivate its kinase (GSK3) because insulin activated a phosphoeniol kinase which adds a head group on lipid

75
Q

What do all growth factor receptors have in common?

A

All these receptors have a Tyr kinase domain on the cytoplasmic side of the plasma membrane

76
Q

What is the JAK-STAT signaling system?

A

Binding of erythropoietin (EPO) causes dimerization of the EPO receptor, which allows JAK, a soluble Tyr kinase, to bind to the internal domain of the receptor and phosphorylate it on several Tyr residues.
In one signaling pathway, the SH2 domain of the STAT protein STAT5 binds to P –Tyr residues on the receptor, bringing it into proximity with JAK. Following phosphorylation of STAT5 by JAK, two STAT5 molecules dimerize, each binding the other’s P –Tyr residue, thus exposing a nuclear localization sequence (NLS) that targets the dimer for transport into the nucleus.
In the nucleus, STAT5 turns on the expression of EPO-controlled genes. In a second signaling pathway, following EPO binding and auto phosphorylation of JAK, the adaptor protein SHC binds the P –Tyr of the receptor, then Grb2 binds SHC and triggers the MAPK cascade, as in the insulin system

77
Q

What does the Guanlyly cyclase do?

A

Catalytic domain converts GTP to cGMP

Works through activation of protein kinase G

78
Q

What is the steps of signal transduction?

A

Insulin binds receptor
Conformation change
Auto phosphoyrlation to active tyrosine
Activates tyrosine kinase
Phosphorylates IRS-1
In glycogen synthase activation – IRS-1 binds to Phospho inotisol pipe kinase 2 Which becomes PIP3
PIP3 bins to protein kinase b and it becomes active
PKB phosphorylates serine son GDK3, and GSK3 folds over on itself and blocks its own active site and is inactivated.
PKB also phosphorylates RAF which is keeping GLUT4 out of the membrane, and now were active and can migrate GLUT4 into the membrane

79
Q

What is PTB Domain?

A

PTB = PHOSPHO TYROSINE BINDING Proteins they only bind phosphorylated tyrosine such as IRS-1

80
Q

What is the difference between an Agonist and an Antagonist?

A

Agonist – binds receptor and mimics the natural ligand. Ex: endotoxin
Antagonist – binds to the receptor and blocks the natural binding; it is an inhibitor

81
Q

What does epinephrine do?

A

Epinephrine is a hormone made in adrenal glands (pair of organs on top of kidneys).
Mediates stress response: mobilization of energy
Binding to receptors in muscle or liver cells induces breakdown of glycogen.
Binding to receptors in adipose cells induces lipid hydrolysis.
Binding to receptors in heart cells increases heart rate.

82
Q

What is the role of phosphodiesteras/PP2A?

A

breaks cGMP/AMP to make AMP using ATP

83
Q

What is the mechanism of desensitization?

A

epinephrine binds to b-adrenergic rector triggering dissociation of a complex from G-protein
bg recruit BARK to membrane, and B-Arestin bind to the phosphorylated terminal of BARK receptor.
the complex enters the cell via endocytosis vesicle and arestin will dissociate and de-phosphorylated the receptor where it will return back to the surface of the cell

84
Q

What inhibits and activates andeyl cyclase?

A

Glucagon activates adenyl cyclase

inhibit adenyl cyclase: Lower cAMP levels, Suppress protein phosphorylation

85
Q

How PKA activated?

A

Activated adenyl cyclase converts ATP to c-AMP which acts as a second messenger to relay the signal from the protein to other parts of the cell.
cAMP (2) activates PKA by binding to its regulatory domain which causes KA to undergo a conformation change and their activation domains are available, thus cAMP is a positive allosteric effector of PKA

86
Q

How do toxins inhibit adenyl cyclase?

A

Chlorotoxin binds to a-g-Protein and inactivates its phosphatase, so it cannot turn quite again so it will always have GTP associated with it which means its always going to turn on adenylyl cyclase, which means PKA will always be active and phosphorylating things it shouldn’t .
Petrosas toxin inhibits the associations w/ adenyl cyclase and we will be making c-AMP all the time
We can have an inhibitory signal that can come in and shut off adenyl cyclase

87
Q

What is the mechanism of PLC

A

G-protein activates a phospholipase C
which means you’re going to cleave something out of the membrane and release a head group of PIP (you’re still a diacyl lipid, but you have lost your head group),
and in the process you will release IP3
which is a soluble molecule that migrates over to the ER.
In the ER there is a calcium channel that it binds to and out comes the calcium that was hid with the SERCUM pump.
Calcium comes with its concentration gradient and it can interact with PKC. Calcium also associates with DHAG which is a second message.
PKC bound to calcium and the membrane, we have a full conformational change to activate PKC
There is a calcium channel in the ER membrane that is open by IP3 and closes when IP3 comes off

88
Q

What is the GPCR mechanism of vision?

A

In the rod, there is rhodopsin (Retinol attached to the protein (rhodopsin) via Schiff base lysine residue) and Absorbs a photon of light in cis-retinol and do a conformational change it to trans-retinol.
G-protein goes to GTP and turns off adenyl cycles so we won’t make anymore cAMP
which means we won’t have any calcium to bind to the channel, and thus the calcium channel closes.
Dropping the number of calcium levels will active the phosphodiesterase to get rid of c-GMP and convert it back to GMP
Because we don’t have anymore c-GMP the sodium-calcium channel is closed
Desensitization – G-protein activates phosphatase and goes back to GDP and its no longer binding the inhibitor, but we have to turn on guanylyl cyclase by the calcium channel that was sending calcium out is still open. When calcium levels drop, guanylyl cyclase starts to make cGMP
We have a Receptor that has the wrong rod associated with it, so we have rhodopsin kinase that gets phosphorylated so we can have Arestin bind to it
which makes it not to be functional which gives time exchange trans- and bring in a new cis and we de-phosphorylate
There is a kinase that phosphorylates this receptor and an Arrestin that dissociates the odorant to the vesicle

89
Q

What is the GPCR mechanism of smell?

A

Odorant arrives at mucous layer and olfactory receptors binds to protein
a dissociates from bg and goes on to activate adenyl cyclase which catalyzed cAMP
cAM-gated cation channels opens and Ca2+ enter, raising internal levels of Ca2+
Ca2+ gated chloride channels open, and the efflux of Cl- depolarizes the sell and triggers electrical signal to the brain
Ca2+ reduces affinity of cation channel for cAMP, lowering its sensitivity for the odorant.
GTP is hydrolized to GDP, and the odorant receptor is phosphorylated and removed.

90
Q

What is the GPCR mechanism of taste?

A

Sugar binds to the receptor, activate g-protein using GTP
and make adenyl cyclase to active CAMP to active PKA which will phosphorylate K+ channel and close it,
leading to a depolarization of the cell sending an electrical signal to the brain
The bitter and sweet receptors work the same way. Arrestin binds and we have the sweet taste removed.

91
Q

Why don’t we need receptors for sour an salty flavors?

A

We don’t need a receptor for salt, we just bring them in on the sodium and potassium channels via membrane potential.
Sour is detected by membrane channels as well, and we don’t need a receptor because it is acid/protons so it does through the membrane.

92
Q

How do toxins affect GTPase?

A

The bacterial toxins that cause cholera and whooping cough (pertussis) are enzymes that catalyze the transfer of the ADP-ribose moiety of NAD+ to an Arg residue of Gs (in the case of cholera toxin, as shown here) or a Cys residue of Gi (pertussis toxin). The
G proteins thus modified fail to respond to normal hormonal stimuli. The pathology of both diseases results from defective regulation of adenyl cyclase and overproduction of cAMP.

93
Q

Why doesn’t the heart utilize glycogen?

A

it doesn’t have any glycogen storage

94
Q

Why do we have the cori cycle?

A

You are metabolizing faster than oxygen can come to the tissue to circuit in the blood so you’re taking glycogen to lactate cus you’re dong fermentation. The lactate goes into the blood and does gluconeogenesis to get glucose into the blood

95
Q

What is “The Wall”?

A

There comes to a point where you cant break down FA anymore b/c you have no more glucose (about the 20 mile mark), and your body has run out of energy – you need carbs to break down fat b/c you need the sugar to feed back into the citric acid cycle. Your body cannot sustain on fat (unless off number FA…feeding in propynyl-co-A to succingyl-coA and send that to TCA)

96
Q

What is the mechanism of leptin?

A

signal is sent to the brain from leptin released in the adipocytes, and norepinephrine b adrenergic receptor exchanges GDP for GTP and we activate AC who turns on PKA which phosphorylates and release FA, and we turn on uncoupling protein to do beta-oxidation to generate some heat. Leptin doesn’t bind to its own tissue, its receptor is in the hypothalamus

97
Q

What is NPY?

A

an orexigenic (appetite-stimulating) hormone THAT Sends signal to eat
Levels rise in starvation and obese mice
it is Inhibited by leptin and insulin

98
Q

What is MSH?

A
an anorexigenic (appetite-suppressing) hormone that Sends signal to stop eating.
Release is stimulated by leptin
99
Q

What is the JAK/STAT of leptin?

A

Leptin binding induces dimerization of the leptin receptor, followed by phosphorylation of specific Tyr residues in the receptor’s cytosolic domain, catalyzed by Janus kinase (JAK).
STATs bound to the phosphorylated leptin receptor are now phosphorylated on Tyr residues by a separate activity of JAK. The
STATs dimerize, binding each other’s P –Tyr residues, and enter the nucleus. Here, they bind specific regulatory regions in the DNA and alter the expression of certain genes.
The products of these genes ultimately influence the organism’s feeding behavior and energy expenditure.

100
Q

What is adiopenctin?

A

a peptide hormone made by adipose tissue (receptors located in the brain) that stimulates AMP Kinase b/c it tells us we are low in energy and therefore we start metabolizing.
AMPK when it phosphorylates inactivates acetyl-coA carboxylase which mean we wont be making mal-coA to do FA and cholesterol synthesis, thus we can get the FA into the mitochondria for oxidation

101
Q

What stimulates AMPK?

A

hypoxia, exercise, extended starvation or fasting

102
Q

What is Ghrelin?

A

Ghrelin is a short-term orexigenic peptide secreted in the stomach that increases hunger sensation

103
Q

What is Prader-Willi Syndrome?

A

Prader-Willi Syndrome associated with high levels of ghrelin, insatiable appetite

104
Q

What is PYY?

A

an appetite-suppressing hormone secreted from the small intestine and colon in response to food entering stomach that is transported to the hypothalamus to Inhibit release of orexigenic NPY Resulting in reduced hunger

105
Q

What is the effect of propionate on obesity?

A

Propionate is known to act on GPCRs of precursor cells, inducing them to become adipocytes and inhibiting lipolysis.

106
Q

Why can steroids diffuse into the membrane?

A

Steroid hormones are soluble enough to get across the membrane b/c they got rid of the alkyl chain so it’s more soluble than cholesterol. It gets into the nuclear membrane, and here is a hormone receptor elements sequence on DNA that is specific to this hormone such as secondary sex characteristics. when bound to a ligand, the receptor is a transcription factor.